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1 May 2014
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Vemurafenib treatment was previously shown to uncover an NRAS-mutant chronic myelomonocytic leukemia (CMML) in a patient with BRAF-mutant metastatic melanoma. Abdel-Wahab and colleagues report that the combination of vemurafenib and the MEK inhibitor cobimetinib blocked vemurafenib-induced CMML proliferation and restored normal white blood cell counts in this patient. Intermittent administration of vemurafenib and cobimetinib has durably maintained a near-complete melanoma response and has prevented CMML progression in association with decreased levels of CMML-derived circulating tumor DNA and reduced ERK activation in monocytes. Intermittent combination RAF and MEK inhibitor therapy may thus be useful for treatment of RAS-driven malignancies arising due to paradoxical activation of wild-type RAF by RAF inhibitors in RAS-mutant cells. For details, please see the article by Abdel-Wahab and colleagues on page 538. - PDF Icon PDF LinkTable of Contents
ISSN 2159-8274
EISSN 2159-8290
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Efficacy of Intermittent Combined RAF and MEK Inhibition in a Patient with Concurrent BRAF- and NRAS-Mutant Malignancies
Omar Abdel-Wahab; Virginia M. Klimek; Alisa A. Gaskell; Agnes Viale; Donavan Cheng; Eunhee Kim; Raajit Rampal; Mark Bluth; James J. Harding; Margaret K. Callahan; Taha Merghoub; Michael F. Berger; David B. Solit; Neal Rosen; Ross L. Levine; Paul B. Chapman
Author Choice
Activating mTOR Mutations in a Patient with an Extraordinary Response on a Phase I Trial of Everolimus and Pazopanib
Nikhil Wagle; Brian C. Grabiner; Eliezer M. Van Allen; Eran Hodis; Susanna Jacobus; Jeffrey G. Supko; Michelle Stewart; Toni K. Choueiri; Leena Gandhi; James M. Cleary; Aymen A. Elfiky; Mary Ellen Taplin; Edward C. Stack; Sabina Signoretti; Massimo Loda; Geoffrey I. Shapiro; David M. Sabatini; Eric S. Lander; Stacey B. Gabriel; Philip W. Kantoff; Levi A. Garraway; Jonathan E. Rosenberg
Research Articles
NUP98–PHF23 Is a Chromatin-Modifying Oncoprotein That Causes a Wide Array of Leukemias Sensitive to Inhibition of PHD Histone Reader Function
Sheryl M. Gough; Fan Lee; Fan Yang; Robert L. Walker; Yeulin J. Zhu; Marbin Pineda; Masahiro Onozawa; Yang Jo Chung; Sven Bilke; Elise K. Wagner; John M. Denu; Yi Ning; Bowen Xu; Gang Greg Wang; Paul S. Meltzer; Peter D. Aplan
A Small-Molecule c-Rel Inhibitor Reduces Alloactivation of T Cells without Compromising Antitumor Activity
Yusuke Shono; Andrea Z. Tuckett; Samedy Ouk; Hsiou-Chi Liou; Grégoire Altan-Bonnet; Jennifer J. Tsai; Jennifer E. Oyler; Odette M. Smith; Mallory L. West; Natalie V. Singer; Ekaterina Doubrovina; Dmitry Pankov; Chandresh V. Undhad; George F. Murphy; Cecilia Lezcano; Chen Liu; Richard J. O'Reilly; Marcel R.M. van den Brink; Johannes L. Zakrzewski
Reduced NF1 Expression Confers Resistance to EGFR Inhibition in Lung Cancer
Elza C. de Bruin; Catherine Cowell; Patricia H. Warne; Ming Jiang; Rebecca E. Saunders; Mary Ann Melnick; Scott Gettinger; Zenta Walther; Anna Wurtz; Guus J. Heynen; Daniëlle A.M. Heideman; Javier Gómez-Román; Almudena García-Castaño; Yixuan Gong; Marc Ladanyi; Harold Varmus; René Bernards; Egbert F. Smit; Katerina Politi; Julian Downward
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